Latin America validation of FACED score in patients with bronchiectasis: an analysis of six cohorts.

BACKGROUND: The FACED score is an easy-to-use multidimensional grading system that has demonstrated an excellent prognostic value for mortality in patients with bronchiectasis. A Spanish group developed the score but no multicenter international validation has yet been published. METHODS: Retrospective and multicenter study conducted in six historical cohorts of patients from Latin America including 651 patients with bronchiectasis. Clinical, microbiological, functional, and radiological variables were collected, following the same criteria used in the original FACED score study. The vital status of all patients was determined in the fifth year of follow-up. The area under ROC curve (AUC-ROC) was used to calculate the predictive power of the FACED score for all-cause and respiratory deaths and both number and severity of exacerbations. The discriminatory power to divide patients into three groups of increasing severity was also analyzed. RESULTS: Mean (SD) age of 48.2 (16), 32.9% of males. The mean FACED score was 2.35 (1.68). During the follow up, 95 patients (14.6%) died (66% from respiratory causes). The AUC ROC to predict all-cause and respiratory mortality were 0.81 (95% CI: 0.77 to 0.85) 0.84 (95% CI: 0.80 to 0.88) respectively, and 0.82 (95% CI: 078-0.87) for at least one hospitalization per year. The division into three score groups separated bronchiectasis into distinct mortality groups (mild: 3.7%; moderate: 20.7% and severe: 48.5% mortality; p < 0.001). CONCLUSIONS: The FACED score was confirmed as an excellent predictor of all-cause and respiratory mortality and severe exacerbations, as well as having excellent discriminative capacity for different degrees of severity in various bronchiectasis populations.

Annual direct medical costs of bronchiectasis treatment: Impact of severity, exacerbations, chronic bronchial colonization and chronic obstructive pulmonary disease coexistence.

Patients with bronchiectasis (BE) present exacerbations that increase with severity of the disease. We aimed to determine the annual cost of BE treatment according to its severity, determined by FACED score, as well as the parameters associated with higher costs. Multicentre historical cohorts study with patients from six hospitals in Spain. The costs arising during the course of a year from maintenance treatment, exacerbations, emergency visits and hospital admissions were analysed. In total, 456 patients were included (56.4% mild BE, 26.8% moderate BE and 16.9% severe BE). The mean cost was €4671.9 per patient, which increased significantly with severity. In mild BE, most of the costs were due to bronchodilators and inhaled steroids; in severe BE, most were due to exacerbations and inhaled antibiotics. Forced expiratory volume in 1 second (FEV1%), age, colonization by Pseudomonas aeruginosa and the number of admissions were independently related to higher costs. The highest costs were found in patients with BE associated with chronic obstructive pulmonary disease, with the most exacerbations and with chronic bronchial colonization by Pseudomonas aeruginosa (PA). In conclusion, BE patients gave rise to high annual costs, and these were doubled on each advance in severity on the FACED score. FEV1%, age, colonization by PA and the number of admissions were independently related to higher costs.

Changes in structural lung disease in cystic fibrosis children over 4 years as evaluated by high-resolution computed tomography.

OBJECTIVES: To compare the worsening of structural lung disease on high-resolution computed tomography (HRCT) with changes in spirometry results in cystic fibrosis (CF) patients, and analyse factors associated with the worsening of structural lung disease over time. METHODS: A total of 31 CF subjects (mean age 11.03 ± 3.67 years old) were prospectively evaluated by two HRCT and spirometry tests performed 4 years apart. HRCT abnormalities were scored using the Bhalla scoring system. Comparisons between changes on HRCT and spirometry were made for all patients, and also for groups categorized by age, sex, genotypic alterations and lung obstruction. RESULTS: The mean HRCT Bhalla scoring, forced expiratory volume in 1 s (FEV1 %pred.) and forced vital capacity (FVC %pred.) were 7.92 ± 3.59, 87.76 ± 20.52 and 96.54 ± 15.12, respectively. There was a significant deterioration in the Bhalla score (p < 0.01) and in certain categories: severity of bronchiectasis, peribronchial thickening, mucous plugging and bronchial divisions. Females had a more pronounced worsening of the Bhalla score than males (p = 0.048). No change over time was found in FEV1 and FVC. Only sex was associated with a deterioration in HRCT. CONCLUSIONS: HRCT Bhalla scoring changes statistically significantly over 4 years, but spirometry results do not. Worsening on HRCT is more evident in females. KEY POINTS: • HRCT Bhalla scoring changes significantly over 4 years, spirometry results do not. • Females experience faster respiratory deterioration than males. • Spirometry results are not associated with deterioration in HRCT.

Mycobacterium avium complex pulmonary disease patients with limited treatment options.

How to identify MAC-PD patients with limited treatment options: an expert consensus https://bit.ly/3QwLQ8T.

Influenza vaccination mitigates severe complications in hospitalized patients: A ten-year observational study, Spain, 2009-2019.

BACKGROUND: Influenza epidemics annually impact a substantial portion of adults worldwide, leading to numerous hospitalizations and fatalities. While the primary goal of vaccination is to prevent influenza virus infection, breakthrough infections can still occur despite vaccination. Evaluating the vaccine effectiveness in preventing severe cases among hospitalized patients is crucial for enhancing vaccination strategies. METHODS: This single-center, observational, cross-sectional, and retrospective study analyzed data from 1,357 patients admitted to La Paz University Hospital for influenza infection between 2009 and 2019. Patients' demographics, clinical variables, comorbidities, vaccination status, and influenza-related outcomes were assessed. Logistic regression analysis was performed to determine the vaccine-independent protective effects. RESULTS: Influenza vaccination independently prevented severe complications, including pneumonia, bacterial superinfection, acute respiratory distress syndrome, and multiple organ failure in hospitalized patients (odds ratio = 0.61, 95% confidence interval: 0.47-0.76). Vaccinated patients had significantly lower intensive care unit admission rates (odds ratio = 0.42, 95% confidence interval: 0.18-0.92). However, there were no significant differences in mortality rates between vaccinated and unvaccinated patients (P = .385). CONCLUSIONS: Our study provides robust evidence supporting the influenza vaccine protective effect against severe outcomes in hospitalized patients during epidemic flu. Vaccination is associated with a significant reduction in severe complications and intensive care unit admissions, emphasizing its importance as a preventive measure. Improving vaccination coverage, especially in specific comorbidities and age groups, could further enhance the vaccine effectiveness in preventing severe influenza cases.

Impact of systemic corticosteroids on hospital length of stay among patients with COVID-19.

BACKGROUND AND OBJECTIVE: The COVID-19 pandemic has posed a threat to hospital capacity due to the high number of admissions, which has led to the development of various strategies to release and create new hospital beds. Due to the importance of systemic corticosteroids in this disease, we assessed their efficacy in reducing the length of stay (LOS) in hospitals and compared the effect of 3 different corticosteroids on this outcome. METHODS: We conducted a real-world, controlled, retrospective cohort study that analysed data from a hospital database that included 3934 hospitalised patients diagnosed with COVID-19 in a tertiary hospital from April to May 2020. Hospitalised patients who received systemic corticosteroids (CG) were compared with a propensity score control group matched by age, sex and severity of disease who did not receive systemic corticosteroids (NCG). The decision to prescribe CG was at the discretion of the primary medical team. RESULTS: A total of 199 hospitalized patients in the CG were compared with 199 in the NCG. The LOS was shorter for the CG than for the NCG (median = 3 [interquartile range = 0-10] vs. 5 [2-8.5]; p = 0.005, respectively), showing a 43% greater probability of being hospitalised ≤ 4 days than > 4 days when corticosteroids were used. Moreover, this difference was only noticed in those treated with dexamethasone (76.3% hospitalised ≤ 4 days vs. 23.7% hospitalised > 4 days [p < 0.001]). Serum ferritin levels, white blood cells and platelet counts were higher in the CG. No differences in mortality or intensive care unit admission were observed. CONCLUSIONS: Treatment with systemic corticosteroids is associated with reduced LOS in hospitalised patients diagnosed with COVID-19. This association is significant in those treated with dexamethasone, but no for methylprednisolone and prednisone.

Relationship between air pollution exposure and the progression of idiopathic pulmonary fibrosis in Madrid: Chronic respiratory failure, hospitalizations, and mortality. A retrospective study.

Introduction: Air pollution has a significant impact on the morbidity and mortality of various respiratory diseases. However, this has not been widely studied in diffuse interstitial lung diseases, specifically in idiopathic pulmonary fibrosis. Objective: In this study we aimed to assess the relationship between four major air pollutants individually [carbon monoxide (CO), nitrogen dioxide (NO2), ozone (O3), and nitrogen oxides (NOx)] and the development of chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis. Methods: We conducted an exploratory retrospective panel study from 2011 to 2020 in 69 patients with idiopathic pulmonary fibrosis from the pulmonary medicine department of a tertiary hospital. Based on their geocoded residential address, levels of each pollutant were estimated 1, 3, 6, 12, and 36 months prior to each event (chronic respiratory failure, hospital admission and mortality). Data was collected from the air quality monitoring stations of the Community of Madrid located <3.5 km (2.2 miles) from each patient's home. Results: The increase in average values of CO [OR 1.62 (1.11-2.36) and OR 1.84 (1.1-3.06)], NO2 [OR 1.64 (1.01-2.66)], and NOx [OR 1.11 (1-1.23) and OR 1.19 (1.03-1.38)] were significantly associated with the probability of developing chronic respiratory failure in different periods. In addition, the averages of NO2, O3, and NOx were significantly associated with the probability of hospital admissions due to respiratory causes and mortality in these patients. Conclusion: Air pollution is associated with an increase in the probability of developing chronic respiratory failure, hospitalization due to respiratory causes and mortality in patients with idiopathic pulmonary fibrosis.

A Profile of Adult Severe Acute Respiratory Syndrome Coronavirus 2 Pneumonia Patients According to Pneumococcal Vaccination Status.

Certain patient profile characteristics, such as preexisting medical conditions, can modify the risk of developing SARS-CoV-2 pneumonia among adults vaccinated and not vaccinated against pneumococcal disease. This retrospective cohort study aimed to quantify the risk of pneumonia caused by SARS-CoV-2 among individuals from 15 to 64 years old with and without pneumococcal vaccination in Spain during the 2020-2021 influenza season and establish a risk profile of patients more likely to develop SARS-CoV-2 pneumonia. Data (demographic information, patient medical history, and lifestyle habits) were gathered both directly from the patient via personal interview and by reviewing electronic medical records. In an adjusted analysis for pneumococcal vaccinated patients, visits to hospital outpatient clinics were protective while visits to primary health care services, being widowed, obese, and not using masks in outdoor open spaces were identified as risk factors. For patients who had not received a pneumococcal vaccine, visits to hospital outpatient clinics were protective, while being overweight or obese, alcohol consumption, and not using masks in outdoor open spaces were identified as risk factors. Concerning comorbidities, in the pneumococcal vaccinated group none were found to be protective but having diabetes or other respiratory diseases were identified as risk factors. In the unvaccinated group, undergoing immunosuppressive treatment and having metastatic tumors were protective factors, while cerebrovascular disease and obesity with a BMI ≥ 40 were risk factors. A similar risk profile for developing SARS-CoV-2 pneumonia in pneumococcal vaccinated and non-vaccinated individuals was found. Generally, vaccinated individuals had a lower risk of developing SARS-CoV-2. The findings suggest that vaccination against S. pneumoniae could prevent and reduce SARS-CoV-2 pneumonia. Additionally, this study has identified individuals with other medical conditions, such as obesity, underweight, diabetes, and a history of respiratory diseases, who are at an increased risk of developing SARS-CoV-2 pneumonia and could benefit from vaccination and supervision.

Air pollution exposure and its effects on idiopathic pulmonary fibrosis: clinical worsening, lung function decline, and radiological deterioration.

Introduction: Major urban pollutants have a considerable influence on the natural history of lung disease. However, this effect is not well known in idiopathic pulmonary fibrosis (IPF). Aim: This study aimed to investigate the effects of air pollution on clinical worsening, lung function, and radiological deterioration in patients with IPF. Methods: This exploratory retrospective cohort study included 69 patients with IPF, monitored from 2011 to 2020. Data on air pollution levels, including carbon monoxide (CO), nitrogen dioxide (NO2), particulate matter ≤ 2.5 µM (PM2.5), ozone (O3), and nitrogen oxides (NOx), were collected from the nearest air quality monitoring stations (<3.5 km from the patients' homes). Patient outcomes such as clinical worsening, lung function decline, and radiological deterioration were assessed over various exposure periods (1, 3, 6, 12, and 36 months). The statistical analyses were adjusted for various factors, including age, sex, smoking status, and treatment. Results: There was an association between higher O3 levels and an increased likelihood of clinical worsening over 6 and 36 months of exposure (odds ratio [OR] and 95% confidence interval [CI] = 1.16 [1.01-1.33] and OR and 95% CI = 1.80 [1.07-3.01], respectively). Increased CO levels were linked to lung function decline over 12-month exposure periods (OR and 95% CI 1.63 = [1.01-2.63]). Lastly, radiological deterioration was significantly associated with higher CO, NO2, and NOx levels over 6-month exposure periods (OR and 95% CI = 2.14 [1.33-3.44], OR and 95% CI = 1.76 [1.15-2.66] and OR and 95% CI = 1.16 [1.03-1.3], respectively). Conclusion: This study suggests that air pollution, specifically O3, CO, NO2, and NOx, could affect clinical worsening, lung function, and radiological outcomes in patients with IPF. These findings highlight the potential role of air pollution in the progression of IPF, emphasizing the need for further research and air quality control measures to mitigate its effects on respiratory health.

The U-Shaped Relationship Between Eosinophil Count and Bronchiectasis Severity: The Effect of Inhaled Corticosteroids.

BACKGROUND: Although a proven relationship exists between the blood eosinophil count (BEC) and the severity of both asthma and COPD, its relationship with bronchiectasis has not been well established. The objective of this study was to analyze the relationship between BEC and the number and severity of exacerbations, and patients' responses to inhaled corticosteroid (IC) treatment in bronchiectasis RESEARCH QUESTION: Does an association exist among BEC, the number of exacerbations and severity of bronchiectasis, and IC treatment? STUDY DESIGN AND METHODS: This was a multicenter (43 centers) prospective observational study derived from the Spanish Bronchiectasis Registry. Patients with proven bronchiectasis and a known BEC were included, whereas those with asthma or antieosinophilic treatments were excluded. Patients were divided into four groups according to the BEC at the time of inclusion in the study in a steady-state situation: (1) eosinopenic bronchiectasis (< 50 eosinophils/µL), (2) low number of eosinophils (51-100/µL), (3) normal number of eosinophils (101-300/µL), and (4) eosinophilic bronchiectasis (> 300 eosinophils/µL). RESULTS: Nine hundred twenty-eight patients finally were included: 123 patients (13.3%) with < 50 eosinophils/µL (eosinopenic group), 164 patients (17.7%) with 50-100 eosinophils/µL, 488 patients (52.6%) with 101-300 eosinophils/µL, and 153 patients (16.5%) with > 300 eosinophils/µL (eosinophilic group). BEC showed a significant U-shaped relationship with severity, exacerbations, lung function, microbiologic profile, and IC treatment (these being higher in the eosinopenic group compared with the eosinophilic group). IC treatment significantly decreased the number and severity of exacerbations only in the group of bronchiectasis patients with > 300 eosinophils/µL. INTERPRETATION: A significant U-shaped relationship was found between BEC and severity and exacerbations in bronchiectasis that was more pronounced in the eosinopenic group. IC treatment decreased the number and severity of exacerbations only in the eosinophilic group.

Peripheral Neutrophil-to-Lymphocyte Ratio in Bronchiectasis: A Marker of Disease Severity.

Most patients with bronchiectasis have a predominantly neutrophilic inflammatory profile, although other cells such as lymphocytes (as controllers of bronchial inflammation) and eosinophils also play a significant pathophysiological role. Easy-to-interpret blood biomarkers with a discriminative capacity for severity or prognosis are needed. The objective of this study was to assess whether the peripheral neutrophil-to-lymphocyte ratio (NLR) is associated with different outcomes of severity in bronchiectasis. A total of 1369 patients with bronchiectasis from the Spanish Registry of Bronchiectasis were included. To compare groups, the sample was divided into increasing quartiles of NLR ratio. Correlations between quantitative variables were established using Pearson's P test. A simple linear regression (with the value of exacerbations as a quantitative variable) was used to determine the independent relationship between the number and severity of exacerbations and the NLR ratio. The area under the curve (AUC)-ROC was used to determine the predictive capacity of the NLR for severe bronchiectasis, according to the different multidimensional scores. Mean age: 69 (15) years (66.3% of women). The mean NLR was 2.92 (2.03). A higher NLR was associated with more severe bronchiectasis (with an especially significant discriminative power for severe forms) according to the commonly used scores (FACED, E-FACED and BSI), as well as with poorer quality of life (SGRQ), more comorbidities (Charlson index), infection by pathogenic microorganisms, and greater application of treatment. Furthermore, the NLR correlated better with severity scores than other parameters of systemic inflammation. Finally, it was an independent predictor of the incident number and severity of exacerbations. In conclusion, the NLR is an inexpensive and easy-to-measure marker of systemic inflammation for determining severity and predicting exacerbations (especially the most severe) in patients with bronchiectasis.

Blood Neutrophil Counts Define Specific Clusters of Bronchiectasis Patients: A Hint to Differential Clinical Phenotypes.

We sought to investigate differential phenotypic characteristics according to neutrophil counts, using a biostatistics approach in a large-cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 1034 patients who met the inclusion criteria were clustered into two groups on the basis of their blood neutrophil levels. Using the Mann-Whitney U test to explore potential differences according to FACED and EFACED scores between the two groups, a neutrophil count of 4990 cells/µL yielded the most balanced cluster sizes: (1) above-threshold (n = 337) and (2) below-threshold (n = 697) groups. Patients above the threshold showed significantly worse lung function parameters and nutritional status, while systemic inflammation levels were higher than in the below-threshold patients. In the latter group, the proportions of patients with mild disease were greater, while a more severe disease was present in the above-threshold patients. According to the blood neutrophil counts using biostatistics analyses, two distinct clinical phenotypes of stable patients with non-CF bronchiectasis were defined. Patients falling into the above-threshold cluster were more severe. Severity was characterized by a significantly impaired lung function parameters and nutritional status, and greater systemic inflammation. Phenotypic profiles of bronchiectasis patients are well defined as a result of the cluster analysis of combined systemic and respiratory variables.

Impact of Chronic Bronchial Infection by Staphylococcus aureus on Bronchiectasis.

The objective of the study was to analyze the factors associated with chronic bronchial infection (CBI) due to methicillin-susceptible Staphylococcus aureus (SA) and assess the clinical impact on severity, exacerbations, hospitalizations, and loss of lung function compared to patients with no isolation of PPMs in a large longitudinal series of patients from the Spanish bronchiectasis registry (RIBRON). Material and methods: A prospective, longitudinal, multicenter study was conducted with patients included in the RIBRON registry between January 2015 and October 2020. The inclusion criteria were an age of 18 years or older and an initial diagnosis of bronchiectasis. Patients recorded in the registry had a situation of clinical stability in the absence of an exacerbation in the four weeks before their inclusion. All patients were encouraged to provide a sputum sample at each visit for microbiological culture. Annual pulmonary function tests were performed according to the national spirometry guidelines. Results: A total of 426 patients were ultimately included in the study: 77 patients (18%) with CBI due to SA and 349 (82%) who did not present any isolation of PPMs in sputum. The mean age was 66.9 years (16.2), and patients 297 (69.7%) were female, with an average BMI of 25.1 (4.7) kg/m2 and an average Charlson index of 1.74 (1.33). The mean baseline value of FEV1 2 L was 0.76, with a mean FEV1% of 78.8% (23.1). One hundred and seventy-two patients (40.4%) had airflow obstruction with FEV1/FVC < 0.7. The mean predictive FACED score was 1.62 (1.41), with a mean value of 2.62 (2.07) for the EFACED score and 7.3 (4.5) for the BSI score. Patients with CBI caused by SA were younger (p < 0.0001), and they had a lower BMI (p = 0.024) and more exacerbations in the previous year (p = 0.019), as well as in the first, second, and third years of follow-up (p = 0.020, p = 0.001, and p = 0.018, respectively). As regards lung function, patients with CBI due to SA had lower levels of FEV1% at the time of inclusion in the registry (p = 0.021), and they presented more frequently with bronchial obstruction (p = 0.042). A lower age (OR: 0.97; 95% CI: 0.94−0.99; p < 0.001), lower FEV1 value% (OR: 0.98; 95% CI: 0.97−0.99; p = 0.035), higher number of affected lobes (OR: 1.53; 95% CI: 1.2−1.95; p < 0.001), and the presence of two or more exacerbations in the previous year (OR: 2.33; 95% CI: 1.15−4.69; p = 0.018) were observed as independent factors associated with CBI due to SA. The reduction in FEv1% in all patients included in the study was −0.31%/year (95% CI: −0.7; −0.07) (p = 0.110). When the reduction in FEv1% is analyzed in the group of patients with CBI due to SA and the group without pathogens, we observed that the reduction in FEV1% was −1.19% (95% CI: −2.09, −0.69) (p < 0.001) in the first group and −0.02% (95% CI: −0.07, −0.01) (p = 0.918) in the second group. According to a linear regression model (mixed effects) applied to determine which factors were associated with a more pronounced reduction in FEv1% in the overall group (including those with CBI due to SA and those with no PPM isolation), age (p = 0.0019), use of inhaled corticosteroids (p = 0.004), presence of CBI due to SA (p = 0.007), female gender (p < 0.001), and the initial value of FEV1 (p < 0.001) were significantly related. Conclusions: Patients with non-CF bronchiectasis with CBI due to SA were younger, with lower FEV1% values, more significant extension of bronchiectasis, and a higher number of exacerbations of mild to moderate symptoms than those with no PPM isolation in respiratory secretions. The reduction in FEV1% was −1.19% (95% CI: −2.09, −0.69) (p < 0.001) in patients with CBI caused by SA.

Systemic Inflammatory Biomarkers Define Specific Clusters in Patients with Bronchiectasis: A Large-Cohort Study.

Differential phenotypic characteristics using data mining approaches were defined in a large cohort of patients from the Spanish Online Bronchiectasis Registry (RIBRON). Three differential phenotypic clusters (hierarchical clustering, scikit-learn library for Python, and agglomerative methods) according to systemic biomarkers: neutrophil, eosinophil, and lymphocyte counts, C reactive protein, and hemoglobin were obtained in a patient large-cohort (n = 1092). Clusters #1-3 were named as mild, moderate, and severe on the basis of disease severity scores. Patients in cluster #3 were significantly more severe (FEV1, age, colonization, extension, dyspnea (FACED), exacerbation (EFACED), and bronchiectasis severity index (BSI) scores) than patients in clusters #1 and #2. Exacerbation and hospitalization numbers, Charlson index, and blood inflammatory markers were significantly greater in cluster #3 than in clusters #1 and #2. Chronic colonization by Pseudomonas aeruginosa and COPD prevalence were higher in cluster # 3 than in cluster #1. Airflow limitation and diffusion capacity were reduced in cluster #3 compared to clusters #1 and #2. Multivariate ordinal logistic regression analysis further confirmed these results. Similar results were obtained after excluding COPD patients. Clustering analysis offers a powerful tool to better characterize patients with bronchiectasis. These results have clinical implications in the management of the complexity and heterogeneity of bronchiectasis patients.

Potent phagocytic activity with impaired antigen presentation identifying lipopolysaccharide-tolerant human monocytes: demonstration in isolated monocytes from cystic fibrosis patients.

Monocyte exposure to LPS induces a transient state in which these cells are refractory to further endotoxin stimulation. This phenomenon, termed endotoxin tolerance (ET), is characterized by a decreased production of cytokines in response to the proinflammatory stimulus. We have established a robust model of ET and have determined the time frame and features of LPS unresponsiveness in cultured human monocytes. A large number of genes transcribed in tolerant monocytes were classified as either "tolerizable" or "nontolerizable" depending on their expression levels during the ET phase. Tolerant monocytes exhibit rapid IL-1R-associated kinase-M (IRAK-M) overexpression, high levels of triggering receptor expressed on myeloid cells-1 (TREM-1) and CD64, and a marked down-regulation of MHC molecules and NF-kappaB2. These cells combine potent phagocytic activity with impaired capability for Ag presentation. We also show that circulating monocytes isolated from cystic fibrosis patients share all the determinants that characterize cells locked in an ET state. These findings identify a new mechanism that contributes to impaired inflammation in cystic fibrosis patients despite a high frequency of infections. Our results indicate that a tolerant phenotype interferes with timing, efficiency, and outcome of the innate immune responses against bacterial infections.

C-Reactive Protein Concentration in Steady-State Bronchiectasis: Prognostic Value of Future Severe Exacerbations. Data From the Spanish Registry of Bronchiectasis (RIBRON).

BACKGROUND: Both systemic inflammation and exacerbations have been associated with greater severity of bronchiectasis. Our objective was to analyze the prognostic value of the peripheral concentration of C-reactive protein (CRP) for the number and severity of exacerbations in patients with bronchiectasis. METHODS: Patients from the Spanish Bronchiectasis Registry (RIBRON) with valid data on their CRP value (in a clinically stable phase) and valid data on exacerbations during the first year of follow-up were included. A logistic regression analysis was used to evaluate the prognostic value of the CRP concentration (divided into tertiles) with the presence of at least one severe exacerbation or at least two mild-moderate exacerbations during the first year of follow-up. RESULTS: 802 patients (mean age: 68.1 [11.1 years], 65% female) were included. Of these, 33.8% and 13%, respectively, presented ≥2 mild-moderate exacerbations or at least one severe exacerbation during the first year of follow-up. The mean value of the CRP was 6.5 (17.6mg/L). Patients with a CRP value between 0.4 and 2.7mg/L (second tertile) and ≥2.7mg/L (third tertile) presented a 2.9 (95%CI: 1.4-5.9) and 4.2 (95%CI: 2.2-8.2) times greater probability, respectively, of experiencing a severe exacerbation than those with <0.4mg/L (control group), regardless of bronchiectasis severity or a history of previous exacerbations. However, the CRP value did not present any prognostic value for the number of mild-moderate exacerbations. CONCLUSIONS: The CRP value was associated with a greater risk of future severe exacerbations but not with mild or moderate exacerbations in patients with steady-state bronchiectasis.

RIBRON: The spanish Online Bronchiectasis Registry. Characterization of the First 1912 Patients. / RIBRON: el registro español informatizado de bronquiectasias. Caracterización de los primeros 1.912 pacientes.

INTRODUCTION: The SEPAR Spanish Bronchiectasis Registry (RIBRON) began as a platform for the collection of longitudinal data on patients with this disease. The objective of this study is to describe its operation and to analyze the characteristics of bronchiectasis patients according to sex. METHODS: A total of 1912 adult patients diagnosed with bronchiectasis in 43 centers were included between February 2015 and 2019. All patients had complete data consisting of at least 79 basic required variables, controlled by an external audit. RESULTS: Mean age was 67.6 (15.2) years; 63.9% were women. The most common symptom was productive cough (78.3%) which was mucopurulent-purulent in 45.9% of cases. The most common etiology was post-infectious (40.4%), while 18.5% were idiopathic. Pseudomonas aeruginosa was the most frequently isolated microorganism (40.4%), of which 25.6% were associated with chronic infection. The annual number of mild-to-moderate/severe exacerbations was 1.62 (1.9)/0.59 (1.3). Half of the patients (50%) presented with airflow obstruction (17% severe). The most frequent radiological localization was lower lobes. The average FACED/E-FACED/BSI values were 2.06 (1.7)/2.67 (2.2)/7.8 (4.5), respectively. Overall, 66.7% of patients were taking inhaled corticosteroids, 19.2% macrolides, and 19.5% inhaled antibiotics. Women presented a less severe profile than men in clinical and functional terms, and a similar infectious, radiological and therapeutic profile. CONCLUSIONS: RIBRON represents an excellent map of the characteristics of bronchiectasis in our country. Two thirds of patients are women who presented lower disease severity as a specific characteristic.

Phenotypic Clustering in Non-Cystic Fibrosis Bronchiectasis Patients: The Role of Eosinophils in Disease Severity.

Whether high blood eosinophil counts may define a better phenotype in bronchiectasis patients, as shown in chronic obstructive pulmonary disease (COPD), remains to be investigated. Differential phenotypic characteristics according to eosinophil counts were assessed using a biostatistical approach in a large cohort study from the Spanish Online Bronchiectasis Registry (RIBRON). The 906 patients who met the inclusion criteria were clustered into two groups on the basis of their eosinophil levels. The potential differences according to the bronchiectasis severity index (BSI) score between two groups (Mann-Whitney U test and eosinophil count threshold: 100 cells/µL) showed the most balanced cluster sizes: above-threshold and below-threshold groups. Patients above the threshold exhibited significantly better clinical outcomes, lung function, and nutritional status, while showing lower systemic inflammation levels. The proportion of patients with mild disease was higher in the above-threshold group, while the below-threshold patients were more severe. Two distinct clinical phenotypes of stable patients with non-cystic fibrosis (CF) bronchiectasis of a wide range of disease severity were established on the basis of blood eosinophil counts using a biostatistical approach. Patients classified within the above-threshold cluster were those exhibiting a mild disease, significantly better clinical outcomes, lung function, and nutritional status while showing lower systemic inflammatory levels. These results will contribute to better characterizing bronchiectasis patients into phenotypic profiles with their clinical implications.

Differences in Nutritional Status and Inflammatory Biomarkers between Female and Male Patients with Bronchiectasis: A Large-Cohort Study.

We hypothesized that systemic inflammatory and nutritional parameters may differ between male and female patients with non-CF bronchiectasis. In a large patient cohort from the Spanish Online Bronchiectasis Registry (RIBRON), clinical features, systemic inflammatory and nutritional parameters were analyzed in male and female patients with bronchiectasis. Lung function, disease severity using several scores, nutritional status, systemic inflammatory parameters, and multivariate regression analyses were performed to identify differences between male and female patients in the target variables. The number of female patients included in the registry was greater than male patients and they had a less severe disease as measured by all three indices of disease severity, a lower degree of airway obstruction, worse diffusion capacity and airway trapping, better nutritional parameters, and lower levels of inflammatory biomarkers. Multivariate regression analysis evidenced that strong relationships were found between female gender and the following variables: total numbers of leukocytes and neutrophils, hemoglobin, hematocrit, creatinine, and body mass index (BMI). Multivariate regression analyses evidenced that nutritional parameters and inflammatory biomarkers may be reliable indicators of gender-related differences in patients with non-CF bronchiectasis. These findings deserve further attention in follow-up investigations in which the potential predictive value of those biomarkers should be thoroughly explored.

Bronchiectasis: A Complex, Heterogeneous Disease. / Las bronquiectasias: una enfermedad compleja y heterogénea.

Most areas of respiratory medicine continue to use an Oslerian approach, based on signs and symptoms, in which the disease is the center of all activity. However, this paradigm is changing. Now that lung diseases have been recognized as heterogeneous and complex, we are moving towards more personalized, precise, patient-oriented medicine. The aim of this review was to define the current state of the knowledge on bronchiectasis, or, more accurately, the bronchiectasis syndrome, as a multidimensional, systemic, heterogeneous, complex disease. We explore the advances that have already been made, and above all the many steps that are still to be taken. We also propose some tools which might facilitate the application of these concepts in clinical practice, and help us continue our journey towards a more holistic view of this disease.